This application for the acquisition of High Performance Computing (HPC) instrumentation is submitted by a Consortium of Investigators (COI) whose NIH-supported research is either entirely dependent on access to, or would benefit greatly from, the availability of such instrumentation. The COI represents a diverse spectrum of users from experienced major users of computation (e.g., Weinstein, Mehler, Shi, Andersen), to members whose research is turning towards computation driven by the underlying science (e.g., Boudker, Wu, Eliezer) and with the guidance of the experienced colleagues and an expert administrative and infrastructure management team headed by the PI. The group represents diversity in academic rank (5 Full Professors, 4 Assistant Professors), as well as gender (6 men, 3 women). Most importantly, the scope, breadth and depth of the science represented by the research of this COI are remarkable. Ranging from molecular biophysics (Andersen, Mehler, Shi, Weinstein) and structural biology (Blanchard, Boudker, Wu) to cell biochemistry (Eliezer), and integrated systems physiology (Clancy), the research addresses disease mechanisms in cancer (Blanchard, Wu), neurodegeneration (Eliezer), drug abuse (Weinstein), and infectious diseases (Wu);it is therefore being supported by several NIH Institutes (NIGMS, NIDA, HBLI, NINDS, NIAID, NIA). The application describes in detail how the requested computational resource, if awarded, will enable significant progress on the important research projects supported by the mentioned NIH institutes in the labs of the COI members. The proposed HPC compute cluster comprises a total of nearly 600 cores dedicated to HPC job processing, and has been tailored to the specific needs of the COI. Visualization and interactive graphics based analysis are major components of the work of this COI and are complemented by the advanced immersive visualization environment (CAVE) that will be integrated with the requested HPC cluster to enable the COI's many projects requiring interactive visualization. Taking advantage of the established human and infrastructure resources made available by the Institute for Computational Biomedicine (ICB) in which the cluster will be housed in a ready, dedicated high-density HPC data center located on the Weill Cornell campus, the cluster will be maintained for the COI by the staff of professionals in the Technology Management Team (TMT) headed by the PI. This professional team is fully supported by the ICB and is dedicated to the efficient maintenance of scientific computing resources and infrastructure in a well organized manner, adhering to the highest professional standards, as detailed in the application. The resource will be supervised by a Management and Advisory Committee (MAC) composed of cluster users, as well as an outside member with computational experience. Integrated with the infrastructure already available to maintain, manage and enhance it with related resources, the availability of the requested equipment will create a scientific and academic synergy within a diverse but highly collaborative group of outstanding investigators. PUBLIC HEALTH RELEVANCE: The high performance computer requested in this application will serve a group of experienced researchers supported by the NIH to make faster progress and deeper discoveries and innovation in their research on the mechanisms of various diseases including cancer, Alzheimer's, Parkinson's, drug abuse and infectious diseases. Their work depends on computers to learn the structure of molecular components of cells and viruses, and to describe mechanisms of heart function and cardiac arrhythmias. The advanced computer will make their work more productive and should lead to fast leads for therapies and prevention.